Improving rational design of animal testing

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Improving rational design of animal testing

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    Multilevel cross-organism transferability analysis (MCOTA)

    Through a multilevel cross-organism transferability analysis (MCOTA) between Homo sapiens and other organisms (e.g., Rattus norvegicus), and vice versa, SPILLO-PBSS makes it possible to assess the reliability of an animal model in advance, for an improved rational design of animal testing and better interpretation of the results. 

    Possible checks and evaluations:
    1 Checking whether the SPILLO-PBSS identified (e.g., in Homo sapiens) potential target proteins of a xenobiotic are also present in the model organism (e.g., Rattus norvegicus)
    2 Calculating the overall sequence identity between the human target protein and the same protein in the model organism
    3 Verifying the local similarity between the xenobiotic binding site within the human target protein and the corresponding target protein of the model organism (e.g., by using SPILLO-PBSS to analyze a 3D model of the model organism protein).

    If carried out in advance, MCOTA makes it possible to avoid unnecessary experiments and to design animal testing in a more targeted way, according to the 3Rs guiding principles. Vice versa, once identified the target proteins of a xenobiotic in a model organism (e.g., Rattus norvegicus) by SPILLO-PBSS, the same analysis can be carried out to assess the transferability of the results to Homo sapiens.

    A representative example of MCOTA can be found in the experimental tests performed to validate a SPILLO-PBSS identified off-target of finasteride (see Paper).